水蛭素对糖尿病足溃疡大鼠创面愈合及血管生成的影响OA

Objective:To investigate the effects of hirudin on wound healing and angiogenesis in diabetic foot ulcer(DFU)rats through regulation of the vascular endothelial growth factor(VEGF)/Notch1 pathway.Methods:The DFU rats were randomly divided into the following groups:control group,model group,low-dose hirudin group,high-dose hirudin group,and inhibitor group,with 10 rats in each group.The wound healing rate of rats in each group was measured.ELISA was performed to measure the expression levels of TNF-α,IL-8,and IL-6 in serum.HE staining was performed to assess path-ological changes in rat wound tissue.Immunohistochemical staining was performed to detect CD34 expression and micro-vascular density(MVD)in wound tissue.Moreover,Western Blot was used to measure the expression levels of VEGF and Notch1 proteins in rat wound tissues.Results:The skin tissue structure of the control group was normal and showed no pathological changes.The distribution of new blood vessels in the model group was relatively sparse,and with a large amount of inflammatory cell infiltration.In the low-dose and high-dose thrombin groups,the number of new blood vessels increased successively,while the inflammatory cell infiltration decreased successively.The inhibitor group showed a fur-ther reduction in neovascularization and an increase in inflammatory cell infiltration.The model group had higher levels of TNF-α,IL-8,and IL-6,and lower wound healing rate,CD34 positivity rate,MVD,expression of VEGF and Notch1 than the control group(P<0.05).The low-dose hirudin and high-dose hirudin groups had lower TNF-α,IL-8,and IL-6,and higher wound healing rates,CD34 positivity rates,MVD,VEGF,and Notch1 than the model group(P<0.05).The inhibitor group had higher levels of TNF-α,IL-8,and IL-6,and lower wound healing rate,CD34 positivity rate,MVD,expression of VEGF and Notch1 compared to the high-dose hirudin group(P<0.05).Conclusion:Hirudin may promote wound healing and angiogenesis in DFU rats by activating the VEGF/Notch1 pathway.